RESUMO
Osteoporosis is a silent disorder with dire consequences, and glucocorticoid use remains the most common iatrogenic cause illustrated by the fact that 30% to 50% of subjects on such long-term therapy experience fractures (Oimomi M, Nakamichi T, Ohara T, Sakai M, Igaki N, Hata F, et al. Fructose-related glycation. Diabetes Res Clin Pract 1989;7:137-9; Reid IR. Glucocorticoid osteoporosis--mechanisms and management. Eur J Endocrinol 1997;137:209-17). By directly affecting bone quality while actively used, glucocorticoids increase the risk of fracture that is independent of a subject's bone density status at the time (Weinstein RS. True strength. J Bone Miner Res 2000;15:621-5). A large number of subjects seen in an allergy and immunology clinic have asthma, chronic rhinosinusitis, or other chronic inflammatory diseases, necessitating the use of these medications and placing them at higher risk for this disease. Data on the effects of both oral and inhaled glucocorticoids on fracture risk are presented. This review concretizes the importance of osteoporosis, its pathophysiology, and provides practical guidelines to prevent and treat it. Management recommendations are tailored to 2 different age groups. The first group consists of children, adolescents, and adults 40 years or younger with a focus on attaining peak bone mass. The second group consists of adults 40 years or older where the use of imaging modalities and Fracture Risk Assessment Tool scores helps triage subjects into fracture risk categories. Those at moderate to high risk require bone-sparing medications. Universal preventive measures for both groups are reviewed. Complicated and severe cases may need additional expertise by an endocrinologist or rheumatologist.
Assuntos
Glucocorticoides , Osteoporose , Adolescente , Adulto , Alergistas , Densidade Óssea , Osso e Ossos , Criança , Glucocorticoides/uso terapêutico , Humanos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controleRESUMO
Non-type 2 inflammation (Non-T2)-mediated asthma is difficult to define due to lack of signature biomarkers. It exists in the absence of T2-high or eosinophilic inflammation and includes neutrophilic and paucigranulocytic subtypes. Several cell types and cytokines, including Th1, Th17, IL-6, and IL-17, contribute to mechanisms of non-T2 asthma. Neutrophil extracellular traps (NETs) and inflammasome activation likely play a role in severe neutrophilic asthma. Several mechanisms lead to uncoupling of airway hyperresponsiveness and remodeling from airway inflammation in paucigranulocytic asthma. Recent research on transcriptomics and proteomics in non-T2 asthma is discussed in this review. Investigations of specific drug therapies for non-T2 asthma have been disappointing, and remain an important area for future clinical studies.
Assuntos
Asma/metabolismo , Inflamação/metabolismo , Asma/tratamento farmacológico , Citocinas/metabolismo , Humanos , Inflamassomos/metabolismo , Inflamação/tratamento farmacológicoAssuntos
Angioedema/tratamento farmacológico , Infecções por Coronavirus/tratamento farmacológico , Glucocorticoides/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Urticária/tratamento farmacológico , Adulto , Angioedema/etiologia , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/diagnóstico , Humanos , Masculino , Obesidade Mórbida , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2 , Resultado do Tratamento , Urticária/etiologiaRESUMO
BACKGROUND: Protocols for HIV care are widely accepted by all international organizations and are proven to reduce mortality and complications from living with HIV. Unfortunately, executing best practice recommendations in Sierra Leone is difficult due to shortages in staff, training, and medications. METHODS: From June 2016 to August 2016, we implemented both an HIV guideline-based clinical evaluation protocol and a patient-centered workflow for TB screening and CD4 testing in the HIV clinic at Koidu Government Hospital (KGH) in rural Sierra Leone. The primary outcome of interest was how often this service center resulted in a clinically significant change in the patients' HIV regimen. Reasons for changing regimen included diagnosis of co-infection with tuberculosis (TB), diagnosis of clinical or presumed immunologic treatment failure of antiretroviral (ART) medications and, need for adherence to weight-based dosing in pediatric patients. FINDINGS: A total of 188 patients with HIV were seen in the clinic; 49 (26%) of these patients had a clinically significant change in their HIV regimen. The most common reason for regimen change was TB co-infection diagnosis in 38 (20%) patients. The other reasons for HIV regimen changes included: eight children whose ART was adjusted to meet appropriate levels for weight-based guidelines, five patients diagnosed with presumed immunologic treatment failure (some also co-infected with tuberculosis), and two patients with a serious side effect to ART. INTERPRETATION: A comprehensive, patient-centric HIV clinic can result in high rates of case detection for tuberculosis and recognition of immunological ART failure.
Assuntos
Antirretrovirais/farmacologia , Infecções por HIV/tratamento farmacológico , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Coinfecção , Feminino , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Serra Leoa/epidemiologia , Falha de Tratamento , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto JovemRESUMO
BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with chronic immune activation, and concurrent sexually transmitted infections (STIs) may increase immune activation. OBJECTIVES: Because HIV-infected youth are at high risk of STIs and little is known about the impact of STIs on immune activation in HIV-infected youth, we conducted an exploratory study examining the association between STIs and systemic inflammation and immune activation among HIV-infected adolescents. STUDY DESIGN: Forty-nine behaviorally infected U.S. youth ages 18-24 years with baseline CD4+ T-cells >350 who maintained viral suppression on therapy by week 48 were included. Evaluation for STIs (herpes simplex virus [HSV], Chlamydia trachomatis, syphilis, Neisseria gonorrhoeae) was conducted as standard of care and reported on case report forms. Measures of T-cell subsets, systemic immune activation, and soluble factors were examined at week 48 for differences between participants with an STI diagnosis during the 48 weeks compared to those without an STI. RESULTS: Forty-three participants (88%) were male; 57% had baseline CD4+ T-cell counts >500 cells/mm3. Eighteen youth were reported to have ≥1 STI. At week 48, participants with STIs demonstrated lower CD4+ T-cell counts (any STI vs. no STI, pâ¯=â¯0.024; HSV vs. no STI, pâ¯=â¯0.022) and evidence of increased systemic immune activation, including higher CD57 intensity, higher HLA-DR intensity, and lower CD28 percentage, when compared to those without STIs. There were no differences in soluble factors between STI groups. CONCLUSIONS: Results indicate novel activation of CD4+ T-cells among HIV-infected youth who have STIs other than HSV, which may contribute to disease progression.
Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Ativação Linfocitária , Infecções Sexualmente Transmissíveis/imunologia , Adolescente , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Subpopulações de Linfócitos T/imunologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Medication-induced angioedema is a bradykinin-mediated process that results from increased production or decreased degradation of bradykinin. These reactions are documented for several cardiac medications including blockers of the renin-angiotensin-aldosterone system (RAAS). Other cardiovascular and diabetes medications further increase the risk of medication-induced angioedema, particularly with concomitant use of RAAS inhibitors. Dipeptidyl peptidase IV inhibitors are a class of oral diabetic agents that affect bradykinin and substance P degradation and therefore can lead to angioedema. Neprilysin inhibitors are a separate class of cardiac medications, which includes sacubitril, and can lead to drug-induced angioedema especially when used in combination with RAAS inhibitors. This article discusses the proposed mechanisms by which these medications cause angioedema and how medication-induced angioedema differs from mast cell-mediated angioedema. It also details how to recognize medication-induced angioedema and the treatment options available.
Assuntos
Angioedema/etiologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antagonistas de Receptor B2 da Bradicinina/uso terapêutico , Cardiomiopatias Diabéticas/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Aminobutiratos , Angioedema/prevenção & controle , Animais , Compostos de Bifenilo , Bradicinina/análogos & derivados , Bradicinina/metabolismo , Combinação de Medicamentos , Humanos , Neprilisina/metabolismo , Sistema Renina-Angiotensina , Substância P/metabolismo , Tetrazóis , ValsartanaRESUMO
BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48. METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. CONCLUSIONS: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.